Scarring Caused by the Percutaneous Approach to Fractures of the Orbit and Orbital Rim.

ABSTRACT: Percutaneous and transconjunctival approaches are commonly used for fractures of the orbit and orbital rim. However, it leaves visible scarring on the face. Although previous studies reported scarring from the percutaneous approach, few reported the degree of such scarring. The authors examined the degree of scarring associated with percutaneous approaches to fractures of the orbit and orbital rim in the Japanese population. The authors reviewed photographs of patients who were treated surgically for fractures of the orbital floor, medial orbital wall, or zygomatic bone via percutaneous approaches to examine the presence of scarring and deformation. In 36% of all patients, the observers were unable to determine the side on which the surgery was performed. Furthermore, the site of scarring was identified accurately in only 20.6% of the cases in which observers were able to identify the surgical side. The authors' study demonstrated that the subciliary approach left minimal scarring under the eyelashes. On the other hand, the medial canthal approach left depressed and wide scarring, whereas pigmentation was apparent in patients who underwent surgery via the lateral eyebrow approach. Similarly, pigmentation under the eyelashes and at the site of secondary incision was common after the subciliary approach.

Pseudoaneurysm of the Maxillary Artery With Prebleeding Warning Signs After Le Fort I Osteotomy.

ABSTRACT: Epistaxis after Le Fort I osteotomy is one of the relatively common postoperative complications. It can be controlled with conservative treatment, such as nasal packing, and will usually improve in a few days. However, if the epistaxis is repeated, the outcome can be life-threatening. A 22-year-old woman underwent Le Fort I osteotomy in order to correct her malocclusion. Postoperatively, pseudoaneurysm was formed in the descending palate artery, causing repeated epistaxis. Then, angiography and embolization were performed. Before the onset of epistaxis, there was discomfort around the nasal area. The patient remained asymptomatic during the 6-month follow-up. Some epistaxis after Le Fort I osteotomy is due to pseudoaneurysm formation in the maxillary artery. It is very rare. The epistaxis is delayed and recurrent. It can cause massive bleeding, and so, requires proper diagnosis and treatment. There may be signs of bleeding as in this case.

Cellular Mechanism Underlying Highly-Active or Antiretroviral Therapy-Induced Lipodystrophy: Atazanavir, a Protease Inhibitor, Compromises Adipogenic Conversion of Adipose-Derived Stem/Progenitor Cells through Accelerating ER Stress-Mediated Cell Death in Differentiating Adipocytes.

Lipodystrophy is a common complication in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART). Previous studies demonstrated that endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR) is involved in lipodystrophy; however, the detailed mechanism has not been fully described in human adipogenic cell lineage. We utilized adipose tissue-derived stem cells (ADSCs) obtained from human subcutaneous adipose tissue, and atazanavir (ATV), a protease inhibitor (PI), was administered to ADSCs and ADSCs undergoing adipogenic conversion. Marked repression of adipogenic differentiation was observed when ATV was administered during 10 days of ADSC culture in adipogenic differentiation medium. Although ATV had no effect on ADSCs, it significantly induced apoptosis in differentiating adipocytes. ATV treatment also caused the punctate appearance of CCAAT-enhancer-binding (C/EBP) protein homologous protein (CHOP), and altered expression of CHOP and GRP78/Bip, which are the representation of ER stress, only in differentiating adipocytes. Administration of UPR inhibitors restored adipogenic differentiation, indicating that ER stress-mediated UPR was induced in differentiating adipocytes in the presence of ATV. We also observed autophagy, which was potentiated in differentiating adipocytes by ATV treatment. Thus, adipogenic cell atrophy leads to ATV-induced lipodystrophy, which is mediated by ER stress-mediated UPR and accelerated autophagy, both of which would cause adipogenic apoptosis. As our study demonstrated for the first time that ADSCs are unsusceptible to ATV and its deleterious effects are limited to the differentiating adipocytes, responsible target(s) for ATV-induced lipodystrophy may be protease(s) processing adipogenesis-specific protein(s).

Biological Features Implies Potential Use of Autologous Adipose-Derived Stem/Progenitor Cells in Wound Repair and Regenerations for the Patients with Lipodystrophy.

A paradigm shift in plastic and reconstructive surgery is brought about the usage of cell-based therapies for wound healing and regeneration. Considering the imitations in the reconstructive surgeries in restoring tissue loss and deficiency, stem cell-based therapy, in particular, has been expected to pave the way for a new solution to the regenerative approaches. Limitations in the reconstructive surgeries in restoring tissue loss and deficiency have paved the way for new regenerative approaches. Among them, adipose-derived stem/progenitor cells (ADSCs)-based therapy could be the most promising clue, since ADSCs have pluripotent differentiation capabilities not only in adipocytes but also in a variety of cell types. Accumulating evidences have indicated that the unfavorable development of adipose-tissue damage, namely, lipodystrophy, is a systemic complication, which is closely related to metabolic abnormality. Considering ADSC-based regenerative medicine should be applied for the treatment of lipodystrophy, it is inevitable to ascertain whether the ADSCs obtained from the patients with lipodystrophy are capable of being used. It will be very promising and realistic if this concept is applied to lipoatrophy; one form of lipodystrophies that deteriorates the patients' quality of life because of excessive loss of soft tissue in the exposed areas such as face and extremities. Since lipodystrophy is frequently observed in the human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART), the present study aims to examine the biological potentials of ADSCs isolated from the HIV-infected patients with lipodystrophy associated with the HAART treatment. Growth properties, adipogenic differentiation, and mitochondrial reactive oxygen species (ROS) production were examined in ADSCs from HIV-infected and HIV-uninfected patients. Our results clearly demonstrated that ADSCs from both patients showed indistinguishable growth properties and potentials for adipocyte differentiation in vitro. Thus, although the number of cases were limited, ADSCs isolated from the patients with lipodystrophy retain sufficient physiological and biological activity for the reconstitution of adipose-tissue, suggesting that ADSCs from the patients with lipodystrophy could be used for autologous ADSC-based regenerative therapy.

Total resection combined with osteotomy is more effective for orbital solitary fibrous tumor excision: a report of three cases.

A solitary fibrous tumor is a neoplasm generally arising from the mesothelial surfaces of the pleura and mesothelium. In this paper, we describe three cases of rare solitary fibrous tumors arising from the orbit and discuss the management of the tumors, including diagnosis and treatment. All three cases were treated by surgical resection and showed satisfactory aesthetic and functional results. For a definitive diagnosis, immunohistochemical staining for proteins such as vimentin, CD34 and bcl-2 and hematoxylin and eosin (H&E) staining for identifying the morphological characteristics of spindle cell tumors with a partially storiform pattern and staghorn vessels are indispensable. The principle of treatment for orbital solitary fibrous tumor is complete resection because the prognosis depends on controlling tumor progression, which can be difficult with chemotherapy and radiotherapy alone.

Novel Application of Cultured Epithelial Autografts (CEA) with Expanded Mesh Skin Grafting Over an Artificial Dermis or Dermal Wound Bed Preparation.

Cultured epithelial autografts (CEA) with highly expanded mesh skin grafts were used for extensive adult burns covering more than 30% of the total body surface area. A prospective study on eight patients assessed subjective and objective findings up to a 12-month follow-up. The results of wound healing for over 1:6 mesh plus CEA, gap 1:6 mesh plus CEA, and 1:3 mesh were compared at 3, 6, and 12 months using extensibility, viscoelasticity, color, and transepidermal water loss by a generalized estimating equation (GEE) or generalized linear mixed model (GLMM). No significant differences were observed among the paired treatments at any time point. At 6 and 12 months, over 1:6 mesh plus CEA achieved significantly better expert evaluation scores by the Vancouver and Manchester Scar Scales (p < 0.01). Extended skin grafting plus CEA minimizes donor resources and the quality of scars is equal or similar to that with conventional low extended mesh slit-thickness skin grafting such as 1:3 mesh. A longitudinal analysis of scars may further clarify the molecular changes of scar formation and pathogenesis.

MiR-142 Is Required for Staphylococcus aureus Clearance at Skin Wound Sites via Small GTPase-Mediated Regulation of the Neutrophil Actin Cytoskeleton.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein translation by binding to complementary target mRNAs. We previously identified two mature members of the miR-142 family, miR-142-5p and miR-142-3p, as inflammation-related miRNAs with potential roles in wound healing. Here, we demonstrated that these two miRNAs are prominently expressed in wound-infiltrated neutrophils and macrophages and play central roles in wound healing. We generated miR-142-/- mice using the exchangeable gene-trap method and showed that healing of Staphylococcus aureus-infected skin wounds was significantly delayed in miR-142-/- mice compared with that in wild-type mice. MiR-142-/- mice exhibited abnormal abscess formation at S. aureus-infected skin wound sites and were also more susceptible to horizontal transmission of wound infections. MiR-142-/- neutrophils showed altered phagocytosis as a consequence of chemotactic behavior, including enhanced F-actin assembly, disturbed cell polarity, and increased cell motility. We showed that these changes were linked to cytoskeletal regulation, and that expression of the small GTPases was markedly increased in miR-142-/- neutrophils. Collectively, our data demonstrate that the miR-142 family is indispensable for protection against S. aureus infection and its clearance at wound sites. MiR-142-3p and miR-142-5p play nonredundant roles in actin cytoskeleton regulation by controlling small GTPase translation in neutrophils at wound sites.

Wound Healing and Angiogenesis through Combined Use of a Vascularized Tissue Flap and Adipose-Derived Stem Cells in a Rat Hindlimb Irradiated Ischemia Model.

BACKGROUND: Treatment of critical limb ischemia is sometimes difficult because of the patient's condition, and some novel approaches are needed. METHODS: The hindlimbs of Sprague-Dawley rats, after 20-Gy x-ray irradiation and surgical occlusion, were divided into four groups: with a superficial fascial flap, 5.0 × 10 adipose-derived stromal/stem cells, and both combined. The rats were tested for laser tissue blood flow, immunohistologic blood vessel density, and foot paw punch hole wound healing. Green fluorescent protein-tagged Sprague-Dawley rats were used for further investigation by cell tracking for 2 weeks. RESULTS: Laser tissue blood flow demonstrated a significant increase in the combined treatment of flap and adipose-derived stem cells at both 1 and 2 weeks. There were no significant differences between the treatment groups treated with flaps alone and those treated with adipose-derived stem cells alone. Wound healing was significantly increased following combined treatment at 1 week, and there was no wound by 2 weeks except for the no-flap and no-adipose-derived stem cell group. The number of vessels depicted by von Willebrand factor showed a significant increase in the combined treatment group, at both 1 week and 2 weeks. In the cell tracking group, at 2 weeks, the green fluorescent protein-tagged adipose-derived stem cells were significantly more positive in the no-flap group than in the flap group. CONCLUSIONS: Adipose-derived stem cells may be a potent cell source in irradiated and occluded limbs by enhancing tissue blood flow and blood vessel density. Adipose-derived stem cells may play an important role in some difficult ischemic conditions in terms of wound healing.

Potency of umbilical cord blood- and Wharton's jelly-derived mesenchymal stem cells for scarless wound healing.

Postnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCB-MSCs) and Wharton's jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections. UCB-MSCs expressed lower levels of the pre-inflammatory cytokines IL1A and IL1B, but higher levels of the extracellular matrix (ECM)-degradation enzymes MMP1 and PLAU compared with WJ-MSCs, suggesting that UCB-MSCs were more likely to favor scarless wound healing. However, we failed to find significant benefits for stem cell therapy in improving wound healing and reducing collagen deposition following the direct injection of 1.0 × 10(5) UCB-MSCs and WJ-MSCs into 5 mm full-thickness skin defect sites in nude mice. Interestingly, the implantation of UCB-MSCs tended to increase the expression of MMP2 and PLAU, two proteases involved in degradation of the extracellular matrix in the wound tissues. Based on our data, UCB-MSCs are more likely to be a favorable potential stem cell source for scarless wound healing, although a better experimental model is required for confirmation.

Adipose-derived stem cell transplantation for therapeutic lymphangiogenesis in a mouse secondary lymphedema model.

AIM: Secondary lymphedema is observed in common after postmalignancy treatment of the breast and the gynecologic organs but effective therapies are not established. Adipose-derived stem cells (ADSCs), which are pluripotent, regenerative in local injection, are tested for murine hindlimb secondary lymphedema by regenerative method. METHODS & RESULTS: Mice were divided into four groups: no ADSCs, 1 × 10(6) ADSCs, 1 × 10(5) ADSCs and 1 × 10(4) ADSCs (each group, n = 20) in a stringent surgical resection and irradiation. Circumferential measurement, lymphatic flow assessment and quantification of lymphatic vessels were performed. RESULTS: The numbers of lymphatic vessels by LYVE-1 immunohistochemistry, and VEGF-C- or VEGFR3-expressing cells were significantly increased in transplanted groups (p < 0.05). CONCLUSION: ADSCs can restore the lymphatic vascular network in secondary lymphedema with increased collecting vessels.

Vascular malformations that were diagnosed as or accompanied by malignant tumors.

BACKGROUND: Vascular malformations can mimic malignant tumors, and the coexistence of both types of lesions can limit and interfere with treatment. A consecutive series of vascular malformations that were treated and evaluated in a single institute and cases involving vascular anomalies combined with malignancies or malignancies that were treated as vascular anomalies were analyzed. OBJECTIVE: Absolute ethanol is used in the treatment and management of vascular malformations and is sometimes administered before a definitive diagnosis has been obtained, despite the fact that some vascular lesions are subsequently revealed to be malignant tumors. This study discusses such cases. MATERIALS AND METHODS: From January 2006 to August 2012, 139 patients were treated for vascular malformations at Nagasaki University Hospital and were followed up for a minimum of 1 year. RESULTS: Four malignant lesions coexisted with or were misdiagnosed as vascular malformations, including a malignant peripheral nerve sheath tumor located in the chest, a hemangiopericytoma of the palate, an adenoid cystic carcinoma of the cheek, and a squamous cell carcinoma of the cheek. Thus, malignant lesions were detected in 2.88% of cases in which vascular malformations were preoperatively diagnosed. CONCLUSION: When treating vascular malformations, it is advisable to be aware of the possibility of malignancy.

Management of vascular malformations.

BACKGROUND: Even though vascular malformations are well categorized, further details are relatively unknown. Of treated patients regarding the frequency, demographic distributions, and other related factors by multivariate regression analyses in proportion to total vascular malformations, methods of treatment and how to manage them have not been elucidated thoroughly. METHODS: From January 2006 to March 2012, consecutively treated patients with vascular anomalies were included in this investigation at least 1-year follow-up. RESULTS: Of the total of 123 cases, 86 females and 37 males, the mean follow-up was 3.5 ± 1.68 years, and the frequency of treatment was 1-8 times (1.8 ± 1.30). Surgery was performed for 22 cases (17.9%) of venous malformations and arteriovenous malformations. In multivariate regression, the frequency of treatment was significantly correlated with the length of follow-up (P < 0.001), age (P < 0.05), and type of malformations (P < 0.05) (R (2) = 0.18). Need for surgery was significantly increased with age at odds ratio (OR) of 1.06 [95% confidence interval (CI), 1.03-1.80] (P < 0.001), and head/face/neck, and upper limb are more performed at OR of 0.24 (95% CI, 0.07-0.85) (P < 0.05). The satisfaction score varied from 1 to 5 (3.9 ± 0.68). Complications occurred in 3 cases (2.4%). In logistic regression of complications, the OR of the satisfaction score was 0.13 (95% CI, 0.02-0.80) (P < 0.05). CONCLUSIONS: Treatment of vascular malformations is an integral part of multidisciplinary approaches. Venous malformations are more frequent in combination surgery, and if there are fewer complications, the patients' satisfaction increases.

Reduced FOXO1 expression accelerates skin wound healing and attenuates scarring.

The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.

Lipid-colloid dressing shows improved reepithelialization, pain relief, and corneal barrier function in split-thickness skin-graft donor wound healing.

Donor-site wound healing was tested with a nonadherent petrolatum- and hydrocolloid-impregnated polyester, a lipid-colloid dressing, and a nonadherent polyester dressing, supplemented with petrolatum manually by a physician onsite. Ten patients, 1 woman and 9 men (22 to 79 years old; average 58.4 ± 17.54 years), were enrolled in this prospective comparison study. The split-thickness skin graft was 14.5 ± 7.49 cm long × 8.2 ± 4.07 cm wide (5.5-27 cm long and 4.0-14.0 wide) and 14/1000 inches (0.356 mm) deep. The degree of reepithelialization in lipid-colloid dressing was significantly better than that in polyester mesh dressing, with 1.7 ± 1.00 and 2.8 ± 0.83 for the lipid-colloid dressing and polyester mesh dressing, respectively (P < .05), and degree of pain was significantly lower in lipid-colloid dressing than that in polyester dressing, 1.7 ± 1.11 and 2.9 ± 1.12 for the lipid-colloid dressing and polyester mesh dressing, respectively (P < .01). In moisture meter analyses, the values of effective contact coefficient and corneal thickness in lipid-colloid at wound healing was significantly smaller than those in polyester mesh (effective contact coefficient: 11.7 ± 1.87% and 15.6 ± 3.09% for lipid-colloid and polyester mesh, respectively, P < .05; corneal thickness: 31.1 ± 6.65 µm and 40.7 ± 8.69 µm for lipid-colloid and polyester mesh, respectively, P < .05). No significant difference was observed at 1 month after healing. The nonadherent lipid-colloid polyester dressing has superior wound healing and pain relief and demonstrates better corneal barrier function delineated by effective contact coefficient and corneal thickness at healing in split-thickness donors.

Vascular anomalies and wounds.

Vascular anomalies comprise vascular tumours and vascular malformations. Some vascular anomalies result in ulcerations and necrosis. In vascular tumours, infantile haemangiomas are predominant and ulceration is demonstrated in up to 16%. In vascular malformations, arteriovenous malformations predominate and frequently demonstrate either primary ulceration or skin necrosis after diagnostic and therapeutic procedures. Various diagnostic and therapeutic imaging methods, such as X-ray, computed tomography (CT), magnetic resonance imaging (MRI), duplex Doppler ultrasound, and angiography, are used to visualize vascular anomalies; angiograms are required when embolization is attempted and blood flow needs to be further investigated. Duplex Doppler ultrasound is useful for routine check-ups as a therapeutic tool; however, it has limited in precision and accuracy. The aim of the present review is to give an overview of wounds related to vascular anomalies, detailing the diagnostic imaging and treatment options.

Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia.

Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders--CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF.

One-stage, simultaneous skin grafting with artificial dermis and basic fibroblast growth factor successfully improves elasticity with maturation of scar formation.

The efficacy of one-stage artificial dermis and skin grafting was tested in a nude rat model. Reconstruction with artificial dermis is usually a two-stage procedure with 2- to 3-week intermission. If one-stage use of artificial dermis and split-thickness skin grafting are effective, the overall burden on patients and the medical cost will markedly decrease. The graft take rate, contraction rate, tissue elasticity, histology, morphometric analysis of the dermal thickness, fibroblast counting, immunohistochemistry of α-smooth muscle actin, matrix metalloproteinase-2, CD31, and F4/80, as well as gelatin zymography, real-time reverse transcriptase polymerase chain reaction for matrix metalloproteinase-2, and electron microscopy, were investigated from day 3 to 3 months postoperatively. The graft take rate was good overall in one-stage artificial dermis and skin grafting groups up to 3 weeks, and the contraction rate was greater in the two-staged artificial dermis and skin grafting group than in the skin grafting alone or one stage of artificial dermis and skin grafting groups. Split-thickness skin grafting with artificial dermis and basic fibroblast growth factor at a concentration of 1 µg/cm(2) showed significantly greater elasticity by Cutometer, and the dermal thickness was significantly thinner, fibroblast counting was significantly greater, and the α-smooth muscle actin expression level was more notable with a more mature blood supply in the dermis and more organized dermal fibrils by electron microscopy at 3 weeks. Thus, one-stage artificial dermis and split-thickness skin grafting with basic fibroblast growth factor show a high graft take rate and better tissue elasticity determined by Cutometer analysis, maturity of the dermis, and increased fibroblast number and blood supply compared to a standard two-stage reconstruction.

Three cases of IgG4-related orbital inflammation presented as unilateral pseudotumor and review of the literature.

IgG4-related disease is an emerging disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. In IgG4-related disease, tumor-like lesions develop in multiple organs, such as the lacrimal gland, salivary gland, lung, pancreas, kidney, and lymph nodes. We report here three cases of IgG4-related orbital inflammation that presented as unilateral pseudotumors. The patients all were men, with an age range of 65-75 years. The patients had been pointed out unilateral intra-orbital masses, and histopathological examinations revealed marked accumulation of IgG4-positive plasma cells (IgG4/IgG ratio: 51.1-71.6%) with fibrosis. But storiform fibrosis was seen in only one case, and no obliterative phlebitis was seen. The serum levels of IgG4 were increased to 178-670 mg/dL. The masses had well-defined homogeneous signal intensities, and they were hypo-intense on T1-weighted MR images and iso-intense on T2-weighted MR images. Gadolinium enhanced mass lesions in two cases. All orbital mass lesions responded well to corticosteroid treatment.

Basic Fibroblast Growth Factor in Scarless Wound Healing.

SIGNIFICANCE: The benefit and role of basic fibroblast growth factor (bFGF) in scarless wound healing in clinical application and basic mechanism are discussed. bFGF is a glycoprotein which is widely used in treating wounds and ulcers. bFGF is easily applicable to any type of wound and leads to a better outcome in color, texture, and firmness. RECENT ADVANCES: The amniotic fluids from human mid-gestational trimester may play an important role in scarless wound healing. To investigate cell properties, we used amniotic fluid to augment both adult and fetal fibroblast mitogenic activities, including DNA synthesis and cell proliferation. Preincubation by both bFGF receptor blocker and anti-bFGF antibody significantly decreases proliferative activity in both adult and fetal skin fibroblasts. CRITICAL ISSUES: Adult wound healing, to some extent, demonstrates scar formation, leading to unfavorable clinical mismatch of tissue texture and color and causing stiffness. bFGF may improve the outcome of wound healing by normalizing the tissue texture and color to the adjacent intact skin and optimally enhancing wound healing. FUTURE DIRECTIONS: bFGF activates ERK and Akt phosphorylation in a dose-dependent manner in both adult and fetal skin fibroblasts, which suggests that bFGF in amniotic fluid plays the most major role in cell proliferation. Application of bFGF from an early wounding stage may lead to better fibroblast proliferation and DNA synthesis through the process of ERK/Akt phosphorylation.

Early experiences with stem cells in treating chronic wounds.

This review provides a thorough and clear discussion on the outcomes of stem cells in treating chronic wounds. With recent technological developments that now allow isolation and culture of stem cells, researchers are able to perform vigorous studies on somatic or adult stem cells. Human and animal stem cell studies are discussed with a focus on the basic process of stem cells in wound healing and the authors' first-hand clinical experience with stem cells used for chronic wound healing.